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PDBsum entry 1dbh

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protein links
Gene regulation PDB id
1dbh
Jmol
Contents
Protein chain
340 a.a. *
Waters ×69
* Residue conservation analysis
PDB id:
1dbh
Name: Gene regulation
Title: Dbl and pleckstrin homology domains from hsos1
Structure: Protein (human sos 1). Chain: a. Fragment: dbl and pleckstrin homology domains. Synonym: son of sevenless protein. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Resolution:
2.30Å     R-factor:   0.229     R-free:   0.269
Authors: S.M.Soisson,J.Kuriyan
Key ref:
S.M.Soisson et al. (1998). Crystal structure of the Dbl and pleckstrin homology domains from the human Son of sevenless protein. Cell, 95, 259-268. PubMed id: 9790532 DOI: 10.1016/S0092-8674(00)81756-0
Date:
17-Dec-98     Release date:   23-Dec-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q07889  (SOS1_HUMAN) -  Son of sevenless homolog 1
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1333 a.a.
340 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     regulation of Rho protein signal transduction   1 term 
  Biochemical function     Rho guanyl-nucleotide exchange factor activity     1 term  

 

 
DOI no: 10.1016/S0092-8674(00)81756-0 Cell 95:259-268 (1998)
PubMed id: 9790532  
 
 
Crystal structure of the Dbl and pleckstrin homology domains from the human Son of sevenless protein.
S.M.Soisson, A.S.Nimnual, M.Uy, D.Bar-Sagi, J.Kuriyan.
 
  ABSTRACT  
 
Proteins containing Dbl homology (DH) domains activate Rho-family GTPases by functioning as specific guanine nucleotide exchange factors. All known DH domains have associated C-terminal pleckstrin homology (PH) domains that are implicated in targeting and regulatory functions. The crystal structure of a fragment of the human Son of sevenless protein containing the DH and PH domains has been determined at 2.3 A resolution. The entirely alpha-helical DH domain is unrelated in architecture to other nucleotide exchange factors. The active site of the DH domain, identified on the basis of sequence conservation and structural features, lies near the interface between the DH and PH domains. The structure suggests that ligation of the PH domain will be coupled structurally to the GTPase binding site.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Domain Structure of the Sos ProteinThe construct used for structure determination is depicted in color. The DH domain is colored blue, the PH domain is yellow, and the linker segment discussed in the text is colored red. The N domain, as described previously, is a structural component of the Ras exchange factor region ([4]). PxxP motifs are SH3-domain binding sites ( [2]).
Figure 3.
Figure 3. Ribbon Diagram of the Structure of the DH and PH Domains from SosAll ribbon diagrams were generated using the program RIBBONS ([7]). Coloring is as depicted in Figure 1; the DH domain is blue, the PH domain is yellow, and the linker segment is red. The conserved regions of the DH domain are labeled and colored as in Figure 1. Magenta, CR1; peach, CR2; olive green, CR3. Red ovals mark the amino- and carboxyl-terminal residues of the DH-PH domains (residues 198 and 550, respectively).
 
  The above figures are reprinted by permission from Cell Press: Cell (1998, 95, 259-268) copyright 1998.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21111786 A.Fernández-Medarde, and E.Santos (2011).
The RasGrf family of mammalian guanine nucleotide exchange factors.
  Biochim Biophys Acta, 1815, 170-188.  
21685891 F.Calvo, V.Sanz-Moreno, L.Agudo-Ibáñez, F.Wallberg, E.Sahai, C.J.Marshall, and P.Crespo (2011).
RasGRF suppresses Cdc42-mediated tumour cell movement, cytoskeletal dynamics and transformation.
  Nat Cell Biol, 13, 819-826.  
20842712 C.Kintscher, S.Wuertenberger, R.Eylenstein, T.Uhlendorf, and Y.Groemping (2010).
Autoinhibition of GEF activity in Intersectin 1 is mediated by the short SH3-DH domain linker.
  Protein Sci, 19, 2164-2174.  
20133692 J.Gureasko, O.Kuchment, D.L.Makino, H.Sondermann, D.Bar-Sagi, and J.Kuriyan (2010).
Role of the histone domain in the autoinhibition and activation of the Ras activator Son of Sevenless.
  Proc Natl Acad Sci U S A, 107, 3430-3435.
PDB code: 3ksy
19560536 M.Aittaleb, G.Gao, C.R.Evelyn, R.R.Neubig, and J.J.Tesmer (2009).
A conserved hydrophobic surface of the LARG pleckstrin homology domain is critical for RhoA activation in cells.
  Cell Signal, 21, 1569-1578.  
19189958 P.García, I.García, F.Marcos, G.R.de Garibay, and Y.Sánchez (2009).
Fission yeast rgf2p is a rho1p guanine nucleotide exchange factor required for spore wall maturation and for the maintenance of cell integrity in the absence of rgf1p.
  Genetics, 181, 1321-1334.  
19037094 P.Garcia, V.Tajadura, and Y.Sanchez (2009).
The Rho1p exchange factor Rgf1p signals upstream from the Pmk1 mitogen-activated protein kinase pathway in fission yeast.
  Mol Biol Cell, 20, 721-731.  
19670212 T.Cierpicki, J.Bielnicki, M.Zheng, J.Gruszczyk, M.Kasterka, M.Petoukhov, A.Zhang, E.J.Fernandez, D.I.Svergun, U.Derewenda, J.H.Bushweller, and Z.S.Derewenda (2009).
The solution structure and dynamics of the DH-PH module of PDZRhoGEF in isolation and in complex with nucleotide-free RhoA.
  Protein Sci, 18, 2067-2079.  
19153575 W.Feng, and M.Zhang (2009).
Organization and dynamics of PDZ-domain-related supramodules in the postsynaptic density.
  Nat Rev Neurosci, 10, 87-99.  
18454158 J.Gureasko, W.J.Galush, S.Boykevisch, H.Sondermann, D.Bar-Sagi, J.T.Groves, and J.Kuriyan (2008).
Membrane-dependent signal integration by the Ras activator Son of sevenless.
  Nat Struct Mol Biol, 15, 452-461.  
19026786 K.D.Swanson, Y.Tang, D.F.Ceccarelli, F.Poy, J.P.Sliwa, B.G.Neel, and M.J.Eck (2008).
The Skap-hom dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch.
  Mol Cell, 32, 564-575.
PDB codes: 1u5g 2otx
18480063 S.Osawa, S.Funamoto, M.Nobuhara, S.Wada-Kakuda, M.Shimojo, S.Yagishita, and Y.Ihara (2008).
Phosphoinositides suppress gamma-secretase in both the detergent-soluble and -insoluble states.
  J Biol Chem, 283, 19283-19292.  
18651097 Y.Narumi, Y.Aoki, T.Niihori, M.Sakurai, H.Cavé, A.Verloes, K.Nishio, H.Ohashi, K.Kurosawa, N.Okamoto, H.Kawame, S.Mizuno, T.Kondoh, M.C.Addor, A.Coeslier-Dieux, C.Vincent-Delorme, K.Tabayashi, M.Aoki, T.Kobayashi, A.Guliyeva, S.Kure, and Y.Matsubara (2008).
Clinical manifestations in patients with SOS1 mutations range from Noonan syndrome to CFC syndrome.
  J Hum Genet, 53, 834-841.  
17847065 A.Bottani, A.Orrico, L.Galli, O.Karam, C.A.Haenggeli, S.Ferey, and B.Conrad (2007).
Unilateral focal polymicrogyria in a patient with classical Aarskog-Scott syndrome due to a novel missense mutation in an evolutionary conserved RhoGEF domain of the faciogenital dysplasia gene FGD1.
  Am J Med Genet A, 143, 2334-2338.  
17143285 A.E.Roberts, T.Araki, K.D.Swanson, K.T.Montgomery, T.A.Schiripo, V.A.Joshi, L.Li, Y.Yassin, A.M.Tamburino, B.G.Neel, and R.S.Kucherlapati (2007).
Germline gain-of-function mutations in SOS1 cause Noonan syndrome.
  Nat Genet, 39, 70-74.  
17540168 J.L.Bos, H.Rehmann, and A.Wittinghofer (2007).
GEFs and GAPs: critical elements in the control of small G proteins.
  Cell, 129, 865-877.  
17215368 K.J.Hwang, F.Mahmoodian, J.A.Ferretti, E.D.Korn, and J.M.Gruschus (2007).
Intramolecular interaction in the tail of Acanthamoeba myosin IC between the SH3 domain and a putative pleckstrin homology domain.
  Proc Natl Acad Sci U S A, 104, 784-789.  
17339331 K.Modzelewska, M.G.Elgort, J.Huang, G.Jongeward, A.Lauritzen, C.H.Yoon, P.W.Sternberg, and N.Moghal (2007).
An activating mutation in sos-1 identifies its Dbl domain as a critical inhibitor of the epidermal growth factor receptor pathway during Caenorhabditis elegans vulval development.
  Mol Cell Biol, 27, 3695-3707.  
17391702 M.K.Chhatriwala, L.Betts, D.K.Worthylake, and J.Sondek (2007).
The DH and PH domains of Trio coordinately engage Rho GTPases for their efficient activation.
  J Mol Biol, 368, 1307-1320.
PDB code: 2nz8
17704816 N.Mitin, L.Betts, M.E.Yohe, C.J.Der, J.Sondek, and K.L.Rossman (2007).
Release of autoinhibition of ASEF by APC leads to CDC42 activation and tumor suppression.
  Nat Struct Mol Biol, 14, 814-823.
PDB code: 2pz1
17606614 R.J.Rojas, M.E.Yohe, S.Gershburg, T.Kawano, T.Kozasa, and J.Sondek (2007).
Galphaq directly activates p63RhoGEF and Trio via a conserved extension of the Dbl homology-associated pleckstrin homology domain.
  J Biol Chem, 282, 29201-29210.  
16421249 P.García, V.Tajadura, I.García, and Y.Sánchez (2006).
Rgf1p is a specific Rho1-GEF that coordinates cell polarization with cell wall biogenesis in fission yeast.
  Mol Biol Cell, 17, 1620-1631.  
17072882 P.García, V.Tajadura, I.García, and Y.Sánchez (2006).
Role of Rho GTPases and Rho-GEFs in the regulation of cell shape and integrity in fission yeast.
  Yeast, 23, 1031-1043.  
15545267 K.Hill, S.Krugmann, S.R.Andrews, W.J.Coadwell, P.Finan, H.C.Welch, P.T.Hawkins, and L.R.Stephens (2005).
Regulation of P-Rex1 by phosphatidylinositol (3,4,5)-trisphosphate and Gbetagamma subunits.
  J Biol Chem, 280, 4166-4173.  
15688002 K.L.Rossman, C.J.Der, and J.Sondek (2005).
GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors.
  Nat Rev Mol Cell Biol, 6, 167-180.  
15775967 O.Llorca, E.Arias-Palomo, J.L.Zugaza, and X.R.Bustelo (2005).
Global conformational rearrangements during the activation of the GDP/GTP exchange factor Vav3.
  EMBO J, 24, 1330-1340.  
15897194 R.E.Joseph, and F.A.Norris (2005).
Substrate specificity and recognition is conferred by the pleckstrin homology domain of the Dbl family guanine nucleotide exchange factor P-Rex2.
  J Biol Chem, 280, 27508-27512.  
15339665 A.Delprato, E.Merithew, and D.G.Lambright (2004).
Structure, exchange determinants, and family-wide rab specificity of the tandem helical bundle and Vps9 domains of Rabex-5.
  Cell, 118, 607-617.
PDB code: 1txu
14999155 A.E.Karnoub, M.Symons, S.L.Campbell, and C.J.Der (2004).
Molecular basis for Rho GTPase signaling specificity.
  Breast Cancer Res Treat, 84, 61-71.  
15274927 D.K.Worthylake, K.L.Rossman, and J.Sondek (2004).
Crystal structure of the DH/PH fragment of Dbs without bound GTPase.
  Structure, 12, 1078-1086.
PDB code: 1rj2
15507210 H.Sondermann, S.M.Soisson, S.Boykevisch, S.S.Yang, D.Bar-Sagi, and J.Kuriyan (2004).
Structural analysis of autoinhibition in the Ras activator Son of sevenless.
  Cell, 119, 393-405.
PDB codes: 1xd2 1xd4 1xdv
15199069 K.R.Skowronek, F.Guo, Y.Zheng, and N.Nassar (2004).
The C-terminal basic tail of RhoG assists the guanine nucleotide exchange factor trio in binding to phospholipids.
  J Biol Chem, 279, 37895-37907.
PDB code: 1nty
15327482 K.Yanagi, T.Kaname, Y.Chinen, and K.Naritomi (2004).
Novel alternative splicing of human faciogenital dysplasia 1 gene.
  Congenit Anom (Kyoto), 44, 137-141.  
14701795 L.Cheng, G.M.Mahon, E.V.Kostenko, and I.P.Whitehead (2004).
Pleckstrin homology domain-mediated activation of the rho-specific guanine nucleotide exchange factor Dbs by Rac1.
  J Biol Chem, 279, 12786-12793.  
15331592 R.Kristelly, G.Gao, and J.J.Tesmer (2004).
Structural determinants of RhoA binding and nucleotide exchange in leukemia-associated Rho guanine-nucleotide exchange factor.
  J Biol Chem, 279, 47352-47362.
PDB codes: 1txd 1x86
15286999 S.J.Silver, F.Chen, L.Doyon, A.W.Zink, and I.Rebay (2004).
New class of Son-of-sevenless (Sos) alleles highlights the complexities of Sos function.
  Genesis, 39, 263-272.  
12917394 D.Pradip, X.Peng, and D.L.Durden (2003).
Rac2 specificity in macrophage integrin signaling: potential role for Syk kinase.
  J Biol Chem, 278, 41661-41669.  
12637530 E.J.Fuentes, A.E.Karnoub, M.A.Booden, C.J.Der, and S.L.Campbell (2003).
Critical role of the pleckstrin homology domain in Dbs signaling and growth regulation.
  J Biol Chem, 278, 21188-21196.  
12885767 G.E.Cozier, D.Bouyoucef, and P.J.Cullen (2003).
Engineering the phosphoinositide-binding profile of a class I pleckstrin homology domain.
  J Biol Chem, 278, 39489-39496.  
14656442 H.Sondermann, S.M.Soisson, D.Bar-Sagi, and J.Kuriyan (2003).
Tandem histone folds in the structure of the N-terminal segment of the ras activator Son of Sevenless.
  Structure, 11, 1583-1593.
PDB code: 1q9c
12637522 K.L.Rossman, L.Cheng, G.M.Mahon, R.J.Rojas, J.T.Snyder, I.P.Whitehead, and J.Sondek (2003).
Multifunctional roles for the PH domain of Dbs in regulating Rho GTPase activation.
  J Biol Chem, 278, 18393-18400.  
12471028 K.Robbe, A.Otto-Bruc, P.Chardin, and B.Antonny (2003).
Dissociation of GDP dissociation inhibitor and membrane translocation are required for efficient activation of Rac by the Dbl homology-pleckstrin homology region of Tiam.
  J Biol Chem, 278, 4756-4762.  
12832783 K.Skowronek, M.Ghumman, Y.Zheng, and N.Nassar (2003).
Crystallization and initial crystal characterization of the N-terminal DH/PH domain of Trio.
  Acta Crystallogr D Biol Crystallogr, 59, 1273-1275.  
12525493 M.A.Baumeister, L.Martinu, K.L.Rossman, J.Sondek, M.A.Lemmon, and M.M.Chou (2003).
Loss of phosphatidylinositol 3-phosphate binding by the C-terminal Tiam-1 pleckstrin homology domain prevents in vivo Rac1 activation without affecting membrane targeting.
  J Biol Chem, 278, 11457-11464.  
12515821 M.Innocenti, E.Frittoli, I.Ponzanelli, J.R.Falck, S.M.Brachmann, P.P.Di Fiore, and G.Scita (2003).
Phosphoinositide 3-kinase activates Rac by entering in a complex with Eps8, Abi1, and Sos-1.
  J Cell Biol, 160, 17-23.  
12429733 W.J.Smith, N.Nassar, A.Bretscher, R.A.Cerione, and P.A.Karplus (2003).
Structure of the active N-terminal domain of Ezrin. Conformational and mobility changes identify keystone interactions.
  J Biol Chem, 278, 4949-4956.
PDB code: 1ni2
  12034765 C.A.Cukras, I.Jeliazkova, and C.G.Nichols (2002).
Structural and functional determinants of conserved lipid interaction domains of inward rectifying Kir6.2 channels.
  J Gen Physiol, 119, 581-591.  
12093730 G.Buchwald, A.Friebel, J.E.Galán, W.D.Hardt, A.Wittinghofer, and K.Scheffzek (2002).
Structural basis for the reversible activation of a Rho protein by the bacterial toxin SopE.
  EMBO J, 21, 3286-3295.
PDB code: 1gzs
11950933 J.C.Patel, A.Hall, and E.Caron (2002).
Vav regulates activation of Rac but not Cdc42 during FcgammaR-mediated phagocytosis.
  Mol Biol Cell, 13, 1215-1226.  
11889037 K.L.Rossman, D.K.Worthylake, J.T.Snyder, D.P.Siderovski, S.L.Campbell, and J.Sondek (2002).
A crystallographic view of interactions between Dbs and Cdc42: PH domain-assisted guanine nucleotide exchange.
  EMBO J, 21, 1315-1326.
PDB codes: 1kz7 1kzg
11856323 M.Lutchman, A.C.Kim, L.Cheng, I.P.Whitehead, S.S.Oh, M.Hanspal, A.A.Boukharov, T.Hanada, and A.H.Chishti (2002).
Dematin interacts with the Ras-guanine nucleotide exchange factor Ras-GRF2 and modulates mitogen-activated protein kinase pathways.
  Eur J Biochem, 269, 638-649.  
12223473 R.Jorge, N.Zarich, J.L.Oliva, M.Azañedo, N.Martínez, X.de la Cruz, and J.M.Rojas (2002).
HSos1 contains a new amino-terminal regulatory motif with specific binding affinity for its pleckstrin homology domain.
  J Biol Chem, 277, 44171-44179.  
11868160 T.C.Hart, Y.Zhang, M.C.Gorry, P.S.Hart, M.Cooper, M.L.Marazita, J.M.Marks, J.R.Cortelli, and D.Pallos (2002).
A mutation in the SOS1 gene causes hereditary gingival fibromatosis type 1.
  Am J Hum Genet, 70, 943-954.  
12388557 Z.Nie, K.T.Stanley, S.Stauffer, K.M.Jacques, D.S.Hirsch, J.Takei, and P.A.Randazzo (2002).
AGAP1, an endosome-associated, phosphoinositide-dependent ADP-ribosylation factor GTPase-activating protein that affects actin cytoskeleton.
  J Biol Chem, 277, 48965-48975.  
11685227 A.E.Karnoub, D.K.Worthylake, K.L.Rossman, W.M.Pruitt, S.L.Campbell, J.Sondek, and C.J.Der (2001).
Molecular basis for Rac1 recognition by guanine nucleotide exchange factors.
  Nat Struct Biol, 8, 1037-1041.  
11511365 A.Mettouchi, S.Klein, W.Guo, M.Lopez-Lago, E.Lemichez, J.K.Westwick, and F.G.Giancotti (2001).
Integrin-specific activation of Rac controls progression through the G(1) phase of the cell cycle.
  Mol Cell, 8, 115-127.  
11238883 F.Bi, B.Debreceni, K.Zhu, B.Salani, A.Eva, and Y.Zheng (2001).
Autoinhibition mechanism of proto-Dbl.
  Mol Cell Biol, 21, 1463-1474.  
11577097 J.T.Snyder, K.L.Rossman, M.A.Baumeister, W.M.Pruitt, D.P.Siderovski, C.J.Der, M.A.Lemmon, and J.Sondek (2001).
Quantitative analysis of the effect of phosphoinositide interactions on the function of Dbl family proteins.
  J Biol Chem, 276, 45868-45875.  
11470431 K.L.Longenecker, M.E.Lewis, H.Chikumi, J.S.Gutkind, and Z.S.Derewenda (2001).
Structure of the RGS-like domain from PDZ-RhoGEF: linking heterotrimeric g protein-coupled signaling to Rho GTPases.
  Structure, 9, 559-569.
PDB code: 1htj
11134331 K.Zhu, B.Debreceni, F.Bi, and Y.Zheng (2001).
Oligomerization of DH domain is essential for Dbl-induced transformation.
  Mol Cell Biol, 21, 425-437.  
11285226 M.L.Knetsch, N.Schäfers, H.Horstmann, and D.J.Manstein (2001).
The Dictyostelium Bcr/Abr-related protein DRG regulates both Rac- and Rab-dependent pathways.
  EMBO J, 20, 1620-1629.  
11448999 P.A.Marignani, and C.L.Carpenter (2001).
Vav2 is required for cell spreading.
  J Cell Biol, 154, 177-186.  
11586298 S.Hadano, C.K.Hand, H.Osuga, Y.Yanagisawa, A.Otomo, R.S.Devon, N.Miyamoto, J.Showguchi-Miyata, Y.Okada, R.Singaraja, D.A.Figlewicz, T.Kwiatkowski, B.A.Hosler, T.Sagie, J.Skaug, J.Nasir, R.H.Brown, S.W.Scherer, G.A.Rouleau, M.R.Hayden, and J.E.Ikeda (2001).
A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2.
  Nat Genet, 29, 166-173.  
11595749 Y.Gao, J.Xing, M.Streuli, T.L.Leto, and Y.Zheng (2001).
Trp(56) of rac1 specifies interaction with a subset of guanine nucleotide exchange factors.
  J Biol Chem, 276, 47530-47541.  
11738596 Y.Zheng (2001).
Dbl family guanine nucleotide exchange factors.
  Trends Biochem Sci, 26, 724-732.  
11084373 A.A.Maghazachi (2000).
Intracellular signaling events at the leading edge of migrating cells.
  Int J Biochem Cell Biol, 32, 931-943.  
11007481 B.Aghazadeh, W.E.Lowry, X.Y.Huang, and M.K.Rosen (2000).
Structural basis for relief of autoinhibition of the Dbl homology domain of proto-oncogene Vav by tyrosine phosphorylation.
  Cell, 102, 625-633.
PDB code: 1f5x
10733575 C.L.de Hoog, W.T.Fan, M.D.Goldstein, M.F.Moran, and C.A.Koch (2000).
Calmodulin-independent coordination of Ras and extracellular signal-regulated kinase activation by Ras-GRF2.
  Mol Cell Biol, 20, 2727-2733.  
10744734 C.V.Carman, L.S.Barak, C.Chen, L.Y.Liu-Chen, J.J.Onorato, S.P.Kennedy, M.G.Caron, and J.L.Benovic (2000).
Mutational analysis of Gbetagamma and phospholipid interaction with G protein-coupled receptor kinase 2.
  J Biol Chem, 275, 10443-10452.  
  10679030 E.Bi, J.B.Chiavetta, H.Chen, G.C.Chen, C.S.Chan, and J.R.Pringle (2000).
Identification of novel, evolutionarily conserved Cdc42p-interacting proteins and of redundant pathways linking Cdc24p and Cdc42p to actin polarization in yeast.
  Mol Biol Cell, 11, 773-793.  
10798396 E.C.Liebl, D.J.Forsthoefel, L.S.Franco, S.H.Sample, J.E.Hess, J.A.Cowger, M.P.Chandler, A.M.Shupert, and M.A.Seeger (2000).
Dosage-sensitive, reciprocal genetic interactions between the Abl tyrosine kinase and the putative GEF trio reveal trio's role in axon pathfinding.
  Neuron, 26, 107-118.  
11080163 G.M.Doody, D.D.Billadeau, E.Clayton, A.Hutchings, R.Berland, S.McAdam, P.J.Leibson, and M.Turner (2000).
Vav-2 controls NFAT-dependent transcription in B- but not T-lymphocytes.
  EMBO J, 19, 6173-6184.  
10835338 G.Scita, P.Tenca, E.Frittoli, A.Tocchetti, M.Innocenti, G.Giardina, and P.P.Di Fiore (2000).
Signaling from Ras to Rac and beyond: not just a matter of GEFs.
  EMBO J, 19, 2393-2398.  
11208126 H.Geissler, R.Ullmann, and T.Soldati (2000).
The tail domain of myosin M catalyses nucleotide exchange on Rac1 GTPases and can induce actin-driven surface protrusions.
  Traffic, 1, 399-410.  
  10655223 I.Rebay, F.Chen, F.Hsiao, P.A.Kolodziej, B.H.Kuang, T.Laverty, C.Suh, M.Voas, A.Williams, and G.M.Rubin (2000).
A genetic screen for novel components of the Ras/Mitogen-activated protein kinase signaling pathway that interact with the yan gene of Drosophila identifies split ends, a new RNA recognition motif-containing protein.
  Genetics, 154, 695-712.  
10940243 J.H.Hurley, and S.Misra (2000).
Signaling and subcellular targeting by membrane-binding domains.
  Annu Rev Biophys Biomol Struct, 29, 49-79.  
10734117 J.L.Kam, K.Miura, T.R.Jackson, J.Gruschus, P.Roller, S.Stauffer, J.Clark, R.Aneja, and P.A.Randazzo (2000).
Phosphoinositide-dependent activation of the ADP-ribosylation factor GTPase-activating protein ASAP1. Evidence for the pleckstrin homology domain functioning as an allosteric site.
  J Biol Chem, 275, 9653-9663.  
10636924 M.R.Kuhne, G.Ku, and A.Weiss (2000).
A guanine nucleotide exchange factor-independent function of Vav1 in transcriptional activation.
  J Biol Chem, 275, 2185-2190.  
11080629 N.Blomberg, E.Baraldi, M.Sattler, M.Saraste, and M.Nilges (2000).
Structure of a PH domain from the C. elegans muscle protein UNC-89 suggests a novel function.
  Structure, 8, 1079-1087.
PDB code: 1fho
10849438 S.P.Hehner, T.G.Hofmann, O.Dienz, W.Droge, and M.L.Schmitz (2000).
Tyrosine-phosphorylated Vav1 as a point of integration for T-cell receptor- and CD28-mediated activation of JNK, p38, and interleukin-2 transcription.
  J Biol Chem, 275, 18160-18171.  
10497244 A.D.Ma, and C.S.Abrams (1999).
Pleckstrin induces cytoskeletal reorganization via a Rac-dependent pathway.
  J Biol Chem, 274, 28730-28735.  
10212259 I.N.Fleming, C.M.Elliott, F.G.Buchanan, C.P.Downes, and J.H.Exton (1999).
Ca2+/calmodulin-dependent protein kinase II regulates Tiam1 by reversible protein phosphorylation.
  J Biol Chem, 274, 12753-12758.  
10431174 J.Cherfils, and P.Chardin (1999).
GEFs: structural basis for their activation of small GTP-binding proteins.
  Trends Biochem Sci, 24, 306-311.  
10489445 K.Longenecker, P.Read, U.Derewenda, Z.Dauter, X.Liu, S.Garrard, L.Walker, A.V.Somlyo, R.K.Nakamoto, A.P.Somlyo, and Z.S.Derewenda (1999).
How RhoGDI binds Rho.
  Acta Crystallogr D Biol Crystallogr, 55, 1503-1515.
PDB code: 1cc0
10521431 M.G.Rudolph, C.Weise, S.Mirold, B.Hillenbrand, B.Bader, A.Wittinghofer, and W.D.Hardt (1999).
Biochemical analysis of SopE from Salmonella typhimurium, a highly efficient guanosine nucleotide exchange factor for RhoGTPases.
  J Biol Chem, 274, 30501-30509.  
10480888 M.Majumdar, T.M.Seasholtz, C.Buckmaster, D.Toksoz, and J.H.Brown (1999).
A rho exchange factor mediates thrombin and Galpha(12)-induced cytoskeletal responses.
  J Biol Chem, 274, 26815-26821.  
10542412 N.Blomberg, E.Baraldi, M.Nilges, and M.Saraste (1999).
The PH superfold: a structural scaffold for multiple functions.
  Trends Biochem Sci, 24, 441-445.  
  10523675 N.Movilla, and X.R.Bustelo (1999).
Biological and regulatory properties of Vav-3, a new member of the Vav family of oncoproteins.
  Mol Cell Biol, 19, 7870-7885.  
10219235 P.Chardin, and F.McCormick (1999).
Brefeldin A: the advantage of being uncompetitive.
  Cell, 97, 153-155.  
  10373510 P.H.Anborgh, X.Qian, A.G.Papageorge, W.C.Vass, J.E.DeClue, and D.R.Lowy (1999).
Ras-specific exchange factor GRF: oligomerization through its Dbl homology domain and calcium-dependent activation of Raf.
  Mol Cell Biol, 19, 4611-4622.  
10485851 S.N.Prokopenko, A.Brumby, L.O'Keefe, L.Prior, Y.He, R.Saint, and H.J.Bellen (1999).
A putative exchange factor for Rho1 GTPase is required for initiation of cytokinesis in Drosophila.
  Genes Dev, 13, 2301-2314.  
10559246 T.Reid, A.Bathoorn, M.R.Ahmadian, and J.G.Collard (1999).
Identification and characterization of hPEM-2, a guanine nucleotide exchange factor specific for Cdc42.
  J Biol Chem, 274, 33587-33593.  
9846881 B.Aghazadeh, K.Zhu, T.J.Kubiseski, G.A.Liu, T.Pawson, Y.Zheng, and M.K.Rosen (1998).
Structure and mutagenesis of the Dbl homology domain.
  Nat Struct Biol, 5, 1098-1107.
PDB code: 1by1
9790522 S.R.Sprang, and D.E.Coleman (1998).
Invasion of the nucleotide snatchers: structural insights into the mechanism of G protein GEFs.
  Cell, 95, 155-158.  
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